Mechanisms of commensal bacteria induced humoral immunity

共生菌诱导体液免疫的机制

• 批准号: 10844798
• 负责人: Joel R Wilmore
• 金额: $ 2.08万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10844798
• 关键词: Affect; Antibodies; Antibody Response; Bacteria; Bone Marrow; Communities; Complex; Diabetes Mellitus; Disease; Equilibrium; Frequencies; Genes; Goals; Health; Human; Humoral Immunities; Hypersensitivity; Immunoglobulin A; Individual; Inflammatory Bowel Diseases; Integration Host Factors; Lamina Propria; Link; Modeling; Mucous Membrane; Obesity; Outcome; Plasma Cells; Production; Property; Research; Sepsis; Serum; Site; Specificity; System; Vision; commensal bacteria; intestinal homeostasis; microbial community; microbiome; novel therapeutics; programs; response; vaccine delivery

Project Summary/Abstract The microbiome affects many aspects of human health and has been linked to diseases such as obesity, inflammatory bowel disease, diabetes, and allergy. The balance between host and commensal bacteria is well maintained in most healthy individuals. One host factor that contributes to intestinal homeostasis is antibody of the IgA subclass. Plasma cells that produce IgA are found in mucosal tissues such as the lamina propria of the gut, but they can also be found in systemic sites including the bone marrow. However, high levels of bone marrow IgA are only found in the presence of certain consortia of bacteria. Increased frequencies of bone marrow IgA-secreting plasma cells are associated with increased concentration of serum IgA that has been shown to be protective in a sepsis model of polymicrobial dissemination. The mechanisms by which bacteria induce systemic IgA responses are unknown. The main goal of this proposal is to take an unbiased approach to defining gene-level mechanisms used by commensal bacteria to induce systemic IgA. Additionally, we will examine how inter-species interactions contribute to systemic IgA specificity. Together, this proposal will provide a framework for understanding how systemic antibody responses are induced in response to commensal bacteria. This understanding could lead to novel therapies aimed at maintaining intestinal homeostasis or using commensal bacteria as a vaccine delivery system. This proposal will support the overall vision of our research program to understand the complex interplay at the interface of bacteria and host by deciphering gene-level mechanisms used by bacteria to induce IgA responses.

项目总结/摘要 微生物组影响人类健康的许多方面，并与疾病有关， 肥胖、炎症性肠病、糖尿病和过敏。主持人与主持人之间的平衡 细菌在大多数健康的个体中保持良好。一个宿主因素，有助于肠道 体内平衡是IgA亚类的抗体。产生IgA的浆细胞存在于粘膜组织中， 如肠道的固有层，但它们也可以在包括骨髓在内的全身部位发现。 然而，高水平的骨髓IgA仅在某些细菌聚生体存在的情况下被发现。 骨髓IgA分泌浆细胞的频率增加与浓度增加相关 血清IgA，已被证明是保护性的脓毒症模型的多微生物传播。的 细菌诱导全身性IgA应答的机制尚不清楚。该提案的主要目标是 采取公正的方法来定义肠道细菌诱导 全身性IgA此外，我们将研究种间相互作用如何有助于全身IgA特异性。 总之，这一建议将提供一个框架，了解如何全身抗体反应， 是由细菌引起的。这种理解可能会导致新的治疗方法， 维持肠道内稳态或使用肠道细菌作为疫苗递送系统。这项建议 将支持我们的研究计划的整体愿景，以了解在接口的复杂的相互作用， 通过破译细菌诱导IgA反应的基因水平机制，